Pde IV inhibitors

Abstract

The purpose is to provide selective PDE IV inhibitors which have a potent anti-asthmatic profile with excellent safety. A compound of the formula (1): 1 wherein A is methylene, lower alkylmethylene, carbonyl, etc., Y is a 5- or 6-membered heteroaryl group containing one or two heteroatoms selected from nitrogen, sulfur and oxygen, Z is i) a fused ring in which any of 5- or 6-membered heteroaryl groups is fused to a benzene ring, or ii) a phenyl group which may be unsubstituted or optionally substituted with one or more members selected from the group consisting of nitro, amino, an amino nitrogen-containing group, etc., provided that when A is methylene, Y is a 5- or 6-membered heteroaryl group selected from the group consisting of pyrrolyl, pyridyl, etc., and Z is a phenyl group which may be unsubstituted or substituted, the substituent on said phenyl group is amino, or an amino nitrogen-containing group; or a pharmaceutically acceptable salt thereof, possesses excellent PDE IV inhibition and is useful as a pharmaceutical drug, preferably an anti-asthmatic, etc.

Description

FIELD OF THE INVENTION[0001] The present invention relates to novel 1,8-naphthyridin-2(1H)-one derivatives that inhibit phosphodiesterase (hereinafter, referred to as "PDE") IV, or pharmaceutically acceptable salts thereof, and to pharmaceutical compositions comprising the same.BACKGROUND OF THE INVENTION[0002] PDEs are enzymes which hydrolyze intracellular cyclic AMP (cAMP) and intracellular cyclic GMP (cGMP) and widely distributed in vivo in various tissues and organs. Up to now, it has been known that PDEs are classified into 7 isoenzyme families, i.e., type I to VII PDEs (PDE I to VII), according to their properties. Among them, PDE IV is known to be an enzyme which is predominantly present in airway smooth muscle cells and a wide variety of inflammatory cells, i.e., neutrophils, eosinophils, lymphocytes, etc. and selectively breaks down cAMP. In addition, it has been known that an elevation of cAMP levels in airway smooth muscle cells leads to relaxation of the airway smooth mu...

AI Technical Summary

Benefits of technology

The present invention relates to a group of compounds called 1,8-naphthyridin-2(1H)-one derivatives, which have been found to selectively inhibit PDE IV, a specific enzyme involved in the regulation of inflammation. These compounds have been produced through a research process and have been found to have various advantages over conventional PDE IV inhibitors, including better pharmacological action and safety. The invention also includes methods for producing these compounds and their pharmaceutically acceptable salts. The technical effects of the invention include the development of new compounds with improved PDE IV inhibitory activity and safety, as well as methods for their production.

Problems solved by technology

Therefore, rolipram has a drawback that it has adverse central side-effects effects such as an emetic action.

Such compound groups are, however, unsatisfactory in view of solving the aforementioned problems.

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